Single giant mediastinal rhabdomyoma as a sole manifestation of TSC in foetus

Abstract

Background. Presence of multiple cardiac rhabdomyomas is one of the major features of Tuberous sclerosis (TSC), but isolated progressing single giant rhabdomyoma is very rare and not typical of TSC. Case report. This report presents family without obvious history of TSC with occurrence of giant mediastinal rhabdomyoma affecting the haemodynamics in male foetus, without other TSC symptoms. Girl from the next gravidity had prenatally detected multiple rhabdomyomas and small subcortical tuber of brain detected after birth. DNA analysis found novel c.4861A>T TSC2 variant and large deletion in TSC2 in tumour tissue from male foetus. The novel TSC2 variant was also present in the girl and her healthy father, in silico analysis suggested its functional effect on TSC2. Brain MRI of the father detected mild TSC specific abnormality. Conclusion. We suggest the novel TSC2 mutation is a cause of mild TSC in this family and has reduced expression. The clinical and molecular findings in this family also emphasize that TSC diagnosis should be also evaluated in case of single giant foetal cardiac rhabdomyoma.

Diagnosis of tuberous sclerosis complex in the fetus

“…Crawford). In the last decades a growing number of case reports have been described in the literature (23,28,(30)(31)(32)(33)(34)(35)(36) along with original case series studies (11,21,24,25,26,22,29) researching the clinical association of cardiac tumors in fetuses with TSC diagnosis. Most studies are small in number and lack long-term follow-up data (22.…”

Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing

“…Different second‐hit variants can be present in different angiofibroma or AML tissues from the same patient with TSC (Ikehata & Ono, 2011 ; Tyburczy et al, 2014 ). Godava et al reported a second‐hit variant in CR that was a large deletion in TSC2 (Godava et al, 2017 ). In our study, only one patient with CR exhibited a second‐hit variant (1/8, 12.5%), in contrast to the percentage of patients with angiofibroma (14/17, 82.4%) or AML (10/32, 31.2%) who have been reported to carry second‐hit variants (Giannikou et al, 2016 ; Tyburczy et al, 2014 ).…”

“…Previous studies have assessed TSC1 / TSC2 somatic variants in angiofibromas, angiomyolipomas (AMLs), and lymphangioleiomyomatosis (LAM) tissue (Lam et al, 2017 ). In 2017, Godava et al detected a c.4861A>T variant and a large deletion in TSC2 in a tumor tissue sample from a single giant CR (Godava et al, 2017 ). This was the first‐ever report of sequencing analysis of CR tissue.…”

New challenges of fetal therapy in Japan

“…A fetoscopic approach, which later developed as fetoscopic endoluminal tracheal occlusion (FETO), replaced open fetal surgery for CDH 15,16 . There are two trends in fetal therapy, one is moving from invasive open surgery to less invasive fetoscopic techniques, while the other is moving from clinical descriptions and retrospective analysis to randomized controlled trials 17 . Following a successful clinical trial, 18 open fetal surgery for myelomeningocele (MMC) continues.…”